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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Liver (Hepatocellular) Cancer Screening (PDQ®) - PDQ Cancer Information Summaries - NCBI Bookshelf</title>
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</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"></div><div class="body"><div class="t">Liver (Hepatocellular) Cancer Screening (PDQ®): Health Professional Version</div><div class="j">PDQ Cancer Information Summaries [Internet]</div></div><div class="tail"></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 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class="fm-sec"><h1 id="_NBK65785_"><span class="title" itemprop="name">Liver (Hepatocellular) Cancer Screening (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contribs">PDQ Screening and Prevention Editorial Board.</p><p class="fm-aai"><a href="#_NBK65785_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062840__95">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about liver (hepatocellular) cancer screening. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062840__96">This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062840__1"><h2 id="_CDR0000062840__1_">Summary of Evidence</h2><p id="CDR0000062840__2">Note: The Summary of Evidence section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.</p><p id="CDR0000062840__109">Other PDQ summaries on <a href="/books/n/pdqcis/CDR0000062906/?report=reader">Primary Liver Cancer Treatment</a> and
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<a href="/books/n/pdqcis/CDR0000062836/?report=reader">Childhood Liver Cancer Treatment</a> are also available.
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</p><div id="CDR0000062840__36"><h3>Benefits</h3><p id="CDR0000062840__37">Based on fair evidence, screening of persons at elevated risk does not result in a decrease in mortality from hepatocellular cancer.</p><p id="CDR0000062840__66"><b>Magnitude of Effect</b>: No reduction in mortality.</p><ul id="CDR0000062840__40" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Randomized controlled trials.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Multiple studies, large number of participants.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Fair.</div></li></ul></div><div id="CDR0000062840__38"><h3>Harms</h3><p id="CDR0000062840__39">Based on fair evidence, screening would result in rare but serious side effects associated with needle aspiration cytology such as needle-track seeding, particularly of lesions more than 2 cm in diameter, and hemorrhage, bile peritonitis, and pneumothorax. Transjugular liver biopsy is rarely associated with major complications such as perforation of the hepatic capsule or cholangitis.</p><p id="CDR0000062840__71"><b>Magnitude of Effect</b>: Good evidence for uncommon but serious harms.</p><ul id="CDR0000062840__67" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Randomized controlled trials and observational studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Multiple studies, large number of participants.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div></div><div id="CDR0000062840__6"><h2 id="_CDR0000062840__6_">Significance</h2><div id="CDR0000062840__7"><h3>Incidence, Mortality, and Risk Factors</h3><p id="CDR0000062840__8">In 2020, liver cancer was the sixth most common cancer and third leading cause of cancer death in the world.[<a class="bibr" href="#CDR0000062840_rl_6_1" rid="CDR0000062840_rl_6_1">1</a>] In the United States, it is estimated that
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there will be 41,630 new cases diagnosed in 2024 and 29,840 deaths due to this disease.[<a class="bibr" href="#CDR0000062840_rl_6_2" rid="CDR0000062840_rl_6_2">2</a>] There is a
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distinct male preponderance among all ethnic groups in the United States.[<a class="bibr" href="#CDR0000062840_rl_6_3" rid="CDR0000062840_rl_6_3">3</a>]</p><p id="CDR0000062840__104">Chronic hepatitis B and C are recognized as the major
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factors worldwide increasing the risk of HCC, with risk being greater in the
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presence of coinfection with hepatitis B virus and hepatitis C virus.[<a class="bibr" href="#CDR0000062840_rl_6_4" rid="CDR0000062840_rl_6_4">4</a>-<a class="bibr" href="#CDR0000062840_rl_6_6" rid="CDR0000062840_rl_6_6">6</a>] The
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incidence of HCC in individuals with chronic hepatitis is as high as 0.46% per
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year. In the United States, chronic hepatitis B and C account for about 30% to
|
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40% of HCC. Chronic hepatitis G infection is not associated with HCC in either
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hepatitis B surface antigen–positive carriers or noncarriers.[<a class="bibr" href="#CDR0000062840_rl_6_7" rid="CDR0000062840_rl_6_7">7</a>]</p><p id="CDR0000062840__9">Cirrhosis is also a risk factor for HCC, irrespective of the etiology of the
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cirrhosis. The annual risk of developing HCC among persons with cirrhosis is
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between 1% and 6%.[<a class="bibr" href="#CDR0000062840_rl_6_5" rid="CDR0000062840_rl_6_5">5</a>] Other risk factors include alcoholic cirrhosis,
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hemochromatosis, alpha-l-antitrypsin deficiency, glycogen storage disease,
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porphyria cutanea tarda, tyrosinemia, and Wilson disease,[<a class="bibr" href="#CDR0000062840_rl_6_8" rid="CDR0000062840_rl_6_8">8</a>] but rarely
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biliary cirrhosis.[<a class="bibr" href="#CDR0000062840_rl_6_9" rid="CDR0000062840_rl_6_9">9</a>] A retrospective case-control study found that features suggestive of nonalcoholic steatohepatitis, including obesity, type 2 diabetes, dyslipidemia, and insulin resistance, were more frequently observed in patients with HCC associated with cryptogenic cirrhosis than in those with HCC of viral or alcohol etiology.[<a class="bibr" href="#CDR0000062840_rl_6_10" rid="CDR0000062840_rl_6_10">10</a>,<a class="bibr" href="#CDR0000062840_rl_6_11" rid="CDR0000062840_rl_6_11">11</a>] Aflatoxins, which are mycotoxins formed by certain <i>Aspergillus </i> species, are
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a frequent contaminant of improperly stored grains and nuts. In parts of
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Africa, the high incidence of HCC in humans may be related to ingestion of
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foods contaminated with aflatoxins. This association, however, is blurred by the
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frequent coexistence of hepatitis B infection in those population groups. The likely etiology of HCC is summarized in the following table.[<a class="bibr" href="#CDR0000062840_rl_6_12" rid="CDR0000062840_rl_6_12">12</a>]
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</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCDR000006284027"><a href="/books/NBK65785/table/CDR0000062840__27/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobCDR000006284027"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="CDR0000062840__27"><a href="/books/NBK65785/table/CDR0000062840__27/?report=objectonly" target="object" rid-ob="figobCDR000006284027">Table</a></h4><p class="float-caption no_bottom_margin"> Likely Etiology of HCC. </p></div></div></div><div id="CDR0000062840_rl_6"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062840_rl_6_1">Sung H, Ferlay J, Siegel RL, et al.: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71 (3): 209-249, 2021. [<a href="https://pubmed.ncbi.nlm.nih.gov/33538338" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33538338</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_2">American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. <a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed December 30, 2024.</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_3">Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. <a href="https://seer.cancer.gov/statistics-network/explorer/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed December 30, 2024.</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_4">Benvegnù L, Fattovich G, Noventa F, et al.: Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. A prospective study. Cancer 74 (9): 2442-8, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7922998" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7922998</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_5">Ikeda K, Saitoh S, Koida I, et al.: A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 18 (1): 47-53, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/7686879" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7686879</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_6">Chiaramonte M, Stroffolini T, Vian A, et al.: Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 85 (10): 2132-7, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10326690" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10326690</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_7">Yuan JM, Govindarajan S, Gao YT, et al.: Prospective evaluation of infection with hepatitis G virus in relation to hepatocellular carcinoma in Shanghai, China. J Infect Dis 182 (5): 1300-3, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11023453" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11023453</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_8">Di Bisceglie AM, Carithers RL, Gores GJ: Hepatocellular carcinoma. Hepatology 28 (4): 1161-5, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9755258" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9755258</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_9">Farinati F, Floreani A, De Maria N, et al.: Hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 21 (3): 315-6, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7530737" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7530737</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_10">Bugianesi E, Leone N, Vanni E, et al.: Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123 (1): 134-40, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12105842" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12105842</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_11">Fattovich G, Stroffolini T, Zagni I, et al.: Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127 (5 Suppl 1): S35-50, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15508101" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15508101</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_6_12">Shiratori Y, Yoshida H, Omata M: Management of hepatocellular carcinoma: advances in diagnosis, treatment and prevention. Expert Rev Anticancer Ther 1 (2): 277-90, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/12113033" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12113033</span></a>]</div></li></ol></div></div><div id="CDR0000062840__10"><h2 id="_CDR0000062840__10_">Evidence of Benefit</h2><div id="CDR0000062840__11"><h3>Rationale for Screening</h3><p id="CDR0000062840__12">The rationale for screening for hepatocellular carcinoma (HCC) is based on the
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|
concept that populations at high risk for HCC, such as those with cirrhosis,
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|
can be identified. However, 20% to 50% of patients presenting with HCC have
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|
previously undiagnosed cirrhosis.[<a class="bibr" href="#CDR0000062840_rl_10_1" rid="CDR0000062840_rl_10_1">1</a>,<a class="bibr" href="#CDR0000062840_rl_10_2" rid="CDR0000062840_rl_10_2">2</a>] These patients would not be recruited
|
|
into a surveillance program if the presence of cirrhosis is used to define a
|
|
target population.[<a class="bibr" href="#CDR0000062840_rl_10_3" rid="CDR0000062840_rl_10_3">3</a>] The modalities potentially available for screening
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|
include serum alpha-fetoprotein (AFP) and ultrasonography.
|
|
Abnormal screening results may lead to liver biopsy for diagnosis. Complications of liver biopsy are reported in 0.06% to 0.32% of patients, and typically occur within the first few hours after the biopsy. </p></div><div id="CDR0000062840__56"><h3>Tumor Markers for the Detection of Hepatocellular Carcinoma</h3><p id="CDR0000062840__57">There are four categories of tumor markers that are currently being used or studied for the detection of hepatocellular carcinoma. These include oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines.[<a class="bibr" href="#CDR0000062840_rl_10_4" rid="CDR0000062840_rl_10_4">4</a>]</p><div id="CDR0000062840__58"><h4>Alpha-fetoprotein</h4><p id="CDR0000062840__59">Serum AFP, a fetal-specific glycoprotein antigen, is the most widely used tumor marker for detecting patients with HCC. The reported sensitivity of AFP for detecting HCC varies widely in both
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|
hepatitis B virus (HBV)-positive and HBV-negative populations, which is attributable to overlap
|
|
between screening and diagnosis study designs.[<a class="bibr" href="#CDR0000062840_rl_10_3" rid="CDR0000062840_rl_10_3">3</a>] When AFP is used for screening of
|
|
high-risk populations, a sensitivity of 39% to 97%, specificity of 76% to 95%,
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|
and a positive predictive value (PPV) of 9% to 32% have been reported.[<a class="bibr" href="#CDR0000062840_rl_10_5" rid="CDR0000062840_rl_10_5">5</a>-<a class="bibr" href="#CDR0000062840_rl_10_9" rid="CDR0000062840_rl_10_9">9</a>] AFP is
|
|
not specific for HCC. Titers also rise in acute or chronic hepatitis,[<a class="bibr" href="#CDR0000062840_rl_10_10" rid="CDR0000062840_rl_10_10">10</a>]
|
|
in pregnancy, and in the presence of germ cell tumors.
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|
</p><p id="CDR0000062840__60">A prospective, 16-year, population-based, observational study of screening for
|
|
HCC included 1,487 Alaska Native individuals chronically infected with
|
|
HBV. The study compared survival among screen-detected patients with HCC with a
|
|
historical comparison group of clinically diagnosed patients with HCC.[<a class="bibr" href="#CDR0000062840_rl_10_8" rid="CDR0000062840_rl_10_8">8</a>] The screening
|
|
program’s target was AFP determination every 6 months. It achieved 97%
|
|
sensitivity and 95% specificity (excluding pregnant women) for HCC. Such high
|
|
sensitivity and specificity have not been found for other high-risk groups,
|
|
such as individuals with cirrhosis.[<a class="bibr" href="#CDR0000062840_rl_10_11" rid="CDR0000062840_rl_10_11">11</a>,<a class="bibr" href="#CDR0000062840_rl_10_12" rid="CDR0000062840_rl_10_12">12</a>] Whether screening actually improved
|
|
survival is not clear. </p><p id="CDR0000062840__97">A case-control study conducted within the U.S. Veterans Affairs (VA) health care system assessed whether screening with AFP and/or ultrasound reduced HCC mortality. The cases were 238 patients with cirrhosis who died of HCC from 2013 to 2015 and who had been in VA care with a diagnosis of cirrhosis for 4 years or more before the diagnosis of HCC. The controls, who did not die of HCC and had also been in VA care for 4 years or more, were matched for date of <i>entry</i> (or focal time) and for age, sex, race, model for end-stage liver disease (MELD) score, and etiology of cirrhosis (mainly hepatitis C virus). The study examiners, blinded to outcome status, used chart extraction to assess exposure to ultrasound and AFP screening. The reason for testing (screening vs. other indication) was assessed, also blinded to outcome. The study found that there was no difference between cases and controls regarding the proportion of patients who underwent screening ultrasound (52.9% vs. 54.2%), AFP screening (74.8% vs. 73.5%), or both. The lack of difference persisted for tests within 1, 2, or 3 years of the outcome.[<a class="bibr" href="#CDR0000062840_rl_10_13" rid="CDR0000062840_rl_10_13">13</a>] Given the paucity of randomized controlled trials and their lack of strength, as noted elsewhere in this section, this case-control study—done with great care to avoid bias—comprised perhaps the strongest evidence about the efficacy of AFP or ultrasound screening; however, it showed no benefit in HCC mortality.</p></div></div><div id="CDR0000062840__16"><h3>Hepatic Ultrasonography</h3><p id="CDR0000062840__17">Limitations in the sensitivity and specificity of AFP in surveillance of high-risk populations led to the use of ultrasonography as an additional method for
|
|
detection of HCC.[<a class="bibr" href="#CDR0000062840_rl_10_3" rid="CDR0000062840_rl_10_3">3</a>] Studies in both healthy hepatitis B
|
|
surface antigen carriers [<a class="bibr" href="#CDR0000062840_rl_10_5" rid="CDR0000062840_rl_10_5">5</a>] and in patients with cirrhosis [<a class="bibr" href="#CDR0000062840_rl_10_7" rid="CDR0000062840_rl_10_7">7</a>] have defined
|
|
the performance characteristics of ultrasound as a screening test for HCC.
|
|
Sensitivity in the former was 71% and in the latter 78%, with 93% specificity.
|
|
The PPVs were 14% and 73%, respectively.
|
|
In a study of patients who were on a waiting list for liver transplant, ultrasonography was found to have a sensitivity of 58%, a specificity of 94%, a negative predictive value of 91%, and a PPV of 68%.[<a class="bibr" href="#CDR0000062840_rl_10_14" rid="CDR0000062840_rl_10_14">14</a>]</p><p id="CDR0000062840__98">A case-control study conducted in the VA population assessed whether screening with AFP and/or ultrasonography reduced HCC mortality. For more information, see the <a href="#CDR0000062840__58">Alpha-fetoprotein</a> section.</p></div><div id="CDR0000062840__18"><h3>Computed Tomography </h3><p id="CDR0000062840__19">Limitations in the sensitivity and specificity of AFP and ultrasonography in
|
|
surveillance of high-risk populations, such as individuals with cirrhosis, led
|
|
to the assessment of computed tomography (CT) as an additional method for
|
|
detection of HCC. Studies in patients with cirrhosis
|
|
suggest that CT may be a more sensitive test for HCC than ultrasonography or AFP more than 20 μg/L.[<a class="bibr" href="#CDR0000062840_rl_10_11" rid="CDR0000062840_rl_10_11">11</a>,<a class="bibr" href="#CDR0000062840_rl_10_12" rid="CDR0000062840_rl_10_12">12</a>]
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|
</p></div><div id="CDR0000062840__20"><h3>Efficacy of Screening and Surveillance Programs</h3><p id="CDR0000062840__32">A controlled trial of 18,816 individuals aged 35 to 59 years with hepatitis B in Shanghai randomly assigned patients to a screening group using AFP and ultrasonography every 6 months versus a usual-care group. HCC mortality was lower in the screened group (83.2 vs. 131.5 per 100,000; mortality rate ratio of 0.63 [95% confidence interval (CI), 0.41–0.98]). While these results are promising, there were problems, including the following:</p><ul id="CDR0000062840__92"><li class="half_rhythm"><div>The results varied in different publications.[<a class="bibr" href="#CDR0000062840_rl_10_15" rid="CDR0000062840_rl_10_15">15</a>]</div></li><li class="half_rhythm"><div> The comparison group was not actively followed.</div></li><li class="half_rhythm"><div>The CI was near 1.0.</div></li><li class="half_rhythm"><div>Intention-to-treat analysis was not used.</div></li><li class="half_rhythm"><div> Assessment of outcome was not blinded.</div></li><li class="half_rhythm"><div>Generalizability to other populations is uncertain.[<a class="bibr" href="#CDR0000062840_rl_10_16" rid="CDR0000062840_rl_10_16">16</a>]</div></li></ul><p id="CDR0000062840__41">A randomized controlled trial studied 5,581 men aged 30 to 69 years who were chronic carriers of HBV between 1989 and 1995 in Qidong County, China. Of these men, 3,712 were randomly assigned to a screening group and 1,869 to a control group. Screening entailed 6-monthly AFP assays, with follow-up of patients having an abnormal (≥20 μg/L) test result. All patients were followed up for liver cancer and/or death. The overall sensitivity and specificity of the program were 55.3% and 86.5%, respectively. In patients who complied with all scheduled screening tests, sensitivity was 80% and specificity was 80.9%. The mortality rate in the screening group (1,138 per 100,000 person-years) was not significantly different from that in the control group (1,114 per 100,000 person-years), although AFP screening resulted in an earlier diagnosis of liver cancer (i.e., percentage of cases in stage I was significantly higher in the screened group [29.0%] than in the control group [6%]).[<a class="bibr" href="#CDR0000062840_rl_10_17" rid="CDR0000062840_rl_10_17">17</a>] A review concluded that the method of measuring AFP was not sensitive enough to detect HCC, affecting interpretation of the negative result of this trial.[<a class="bibr" href="#CDR0000062840_rl_10_15" rid="CDR0000062840_rl_10_15">15</a>]</p></div><div id="CDR0000062840_rl_10"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062840_rl_10_1">Zaman SN, Johnson PJ, Williams R: Silent cirrhosis in patients with hepatocellular carcinoma. Implications for screening in high-incidence and low-incidence areas. Cancer 65 (7): 1607-10, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2155700" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2155700</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_2">Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Liver Cancer Study Group of Japan. Ann Surg 211 (3): 277-87, 1990. [<a href="/pmc/articles/PMC1358432/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1358432</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/2155591" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2155591</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_3">Collier J, Sherman M: Screening for hepatocellular carcinoma. Hepatology 27 (1): 273-8, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9425947" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9425947</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_4">Zhou L, Liu J, Luo F: Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol 12 (8): 1175-81, 2006. [<a href="/pmc/articles/PMC4124425/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4124425</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16534867" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16534867</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_5">Sherman M, Peltekian KM, Lee C: Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 22 (2): 432-8, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7543434" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7543434</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_6">Oka H, Tamori A, Kuroki T, et al.: Prospective study of alpha-fetoprotein in cirrhotic patients monitored for development of hepatocellular carcinoma. Hepatology 19 (1): 61-6, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7506227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7506227</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_7">Pateron D, Ganne N, Trinchet JC, et al.: Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis. J Hepatol 20 (1): 65-71, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7515408" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7515408</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_8">McMahon BJ, Bulkow L, Harpster A, et al.: Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology 32 (4 Pt 1): 842-6, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11003632" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11003632</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_9">Soresi M, Magliarisi C, Campagna P, et al.: Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res 23 (2C): 1747-53, 2003 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/12820452" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12820452</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_10">Di Bisceglie AM, Hoofnagle JH: Elevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B. Cancer 64 (10): 2117-20, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2478280" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2478280</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_11">Chalasani N, Horlander JC, Said A, et al.: Screening for hepatocellular carcinoma in patients with advanced cirrhosis. Am J Gastroenterol 94 (10): 2988-93, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10520857" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10520857</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_12">Peterson MS, Baron RL, Marsh JW, et al.: Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation. Radiology 217 (3): 743-9, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11110938" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11110938</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_13">Moon AM, Weiss NS, Beste LA, et al.: No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients With Cirrhosis. Gastroenterology 155 (4): 1128-1139.e6, 2018. [<a href="/pmc/articles/PMC6180323/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6180323</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29981779" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29981779</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_14">Dodd GD, Miller WJ, Baron RL, et al.: Detection of malignant tumors in end-stage cirrhotic livers: efficacy of sonography as a screening technique. AJR Am J Roentgenol 159 (4): 727-33, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1326883" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1326883</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_15">Aghoram R, Cai P, Dickinson JA: Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B. Cochrane Database Syst Rev 9: CD002799, 2012. [<a href="/pmc/articles/PMC6464874/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6464874</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22972059" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22972059</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_16">Zhang BH, Yang BH, Tang ZY: Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 130 (7): 417-22, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15042359" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15042359</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062840_rl_10_17">Chen JG, Parkin DM, Chen QG, et al.: Screening for liver cancer: results of a randomised controlled trial in Qidong, China. J Med Screen 10 (4): 204-9, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/14738659" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14738659</span></a>]</div></li></ol></div></div><div id="CDR0000062840__76"><h2 id="_CDR0000062840__76_">Evidence of Harms</h2><p id="CDR0000062840__77">Two kinds of harms or complications may result from screening. Direct harms may result from complications of liver biopsy done as part of the diagnostic workup. Such complications are reported in 0.06% to 0.32% of patients, and typically occur within the first few hours after the biopsy. Complications include hemorrhage, bile peritonitis, penetration of viscera, and pneumothorax. Rarely, death occurs as a direct result of liver biopsy (0.009%–0.12%). About one third of patients experience pain at the site of entry, in the right upper quadrant, or in the right shoulder.[<a class="bibr" href="#CDR0000062840_rl_76_1" rid="CDR0000062840_rl_76_1">1</a>] Needle aspiration cytology and liver biopsy are rarely associated with needle-track implantation of malignant cells. Lead-time bias (earlier diagnosis in the natural
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history of hepatocellular carcinoma [HCC] rather than improved survival from earlier diagnosis and
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treatment), length bias (earlier detection of slower-growing and less
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aggressive tumors through screening), and/or overdiagnosis of HCC (detection of
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tumors that will not affect morbidity or mortality) may wholly or partially
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account for the improved 5-year and 10-year survival rates reported.</p><div id="CDR0000062840_rl_76"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062840_rl_76_1">Tobkes AI, Nord HJ: Liver biopsy: review of methodology and complications. Dig Dis 13 (5): 267-74, 1995 Sep-Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/8542662" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8542662</span></a>]</div></li></ol></div></div><div id="CDR0000062840__23"><h2 id="_CDR0000062840__23_">Latest Updates to This Summary (03/06/2024)</h2><p id="CDR0000062840__26">The PDQ cancer information summaries are reviewed regularly and updated as
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new information becomes available. This section describes the latest
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changes made to this summary as of the date above.</p><p id="CDR0000062840__111">
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<b>
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<a href="#CDR0000062840__6">Significance</a>
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</b>
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</p><p id="CDR0000062840__112">Updated <a href="#CDR0000062840__8">statistics</a> with estimated new cases and deaths for 2024 (cited American Cancer Society as reference 2).</p><p id="CDR0000062840__disclaimerHP_3">This summary is written and maintained by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/screening-prevention" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Screening and Prevention Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062840__AboutThis_1">About This PDQ Summary</a> and <a href="https://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® Cancer Information for Health Professionals</a> pages.
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</p></div><div id="CDR0000062840__AboutThis_1"><h2 id="_CDR0000062840__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062840__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062840__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about liver (hepatocellular) cancer screening. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062840__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062840__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/screening-prevention" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Screening and Prevention Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062840__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062840__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062840__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p id="CDR0000062840__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062840__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062840__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a <a href="/books/n/pdqcis/CDR0000304747/?report=reader">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062840__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062840__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062840__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062840__AboutThis_15">PDQ® Screening and Prevention Editorial Board. PDQ Liver (Hepatocellular) Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/liver/hp/liver-screening-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/liver/hp/liver-screening-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389228]</p><p id="CDR0000062840__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062840__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062840__AboutThis_19">The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062840__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062840__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div><div class="fm-sec"><h2 id="_NBK65785_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">PDQ Screening and Prevention Editorial Board</span>.</p><h3>Publication History</h3><p class="small">Published online: March 6, 2024.</p><h3>Version History</h3><ul class="simple-list" style="padding:0"><li><span class="bk_col_itm">NBK65785.15</span> March 6, 2024 (Displayed Version)</li><li><span class="bk_col_itm"><a href="/books/NBK65785.14/?report=reader">NBK65785.14</a></span> September 1, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65785.13/?report=reader">NBK65785.13</a></span> May 2, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65785.12/?report=reader">NBK65785.12</a></span> April 29, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65785.11/?report=reader">NBK65785.11</a></span> July 8, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65785.10/?report=reader">NBK65785.10</a></span> April 15, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65785.9/?report=reader">NBK65785.9</a></span> March 25, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65785.8/?report=reader">NBK65785.8</a></span> April 22, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65785.7/?report=reader">NBK65785.7</a></span> February 21, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65785.6/?report=reader">NBK65785.6</a></span> March 15, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65785.5/?report=reader">NBK65785.5</a></span> December 6, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65785.4/?report=reader">NBK65785.4</a></span> April 12, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65785.3/?report=reader">NBK65785.3</a></span> March 17, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65785.2/?report=reader">NBK65785.2</a></span> April 5, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65785.1/?report=reader">NBK65785.1</a></span> February 12, 2015</li></ul><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>PDQ Screening and Prevention Editorial Board. Liver (Hepatocellular) Cancer Screening (PDQ®): Health Professional Version. 2024 Mar 6. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobCDR000006284027"><div id="CDR0000062840__27" class="table"><h3><span class="title"> Likely Etiology of HCC</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65785/table/CDR0000062840__27/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062840__27_lrgtbl__"><table class="no_top_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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<b>Causative Agents</b>
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<b>Dominant Geographical Area</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Hepatitis B virus </td><td colspan="1" rowspan="1" style="vertical-align:top;">Asia and Africa</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Hepatitis C virus </td><td colspan="1" rowspan="1" style="vertical-align:top;">Europe, United States, and Japan</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Alcohol</td><td colspan="1" rowspan="1" style="vertical-align:top;">Europe and United States</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Aflatoxins</td><td colspan="1" rowspan="1" style="vertical-align:top;">East Asia and Africa</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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